Asymmetric Synthesis of Cα-methyl-γ- and δ-Amino Acids From a Common Synthon and Evaluation of Thionyl Chloride Assisted Peptide Esterifications

Cα-methyl-γ- and δ-unnatural amino acids (UAAs) are important class of biomolecules used extensively as structural scaffolds, peptidomimetics, and in the development of pharmaceuticals. Due to steric congestion surrounding the quaternary center, asymmetric preparation of α,α-disubstituted UAAs are synthetically challenging. Herein, two methods for the synthesis of chiral synthons to prepare Cα-methyl-γ- and -δ-UAAs are reported. A crucial step in both strategies includes an enzymatic hydrolysis of prochiral malonic esters with pig liver esterase (PLE). The first method utilizes the Meyer Schuster rearrangement to prepare α,β-unsaturated diesters synthons, but the preparation of the precursor propargyl alcohol decomposes into uncontrollable retro-aldol products. Alternatively, synthons 3-(hydroxymethyl)-3-methylpyrrolidin-2-one and piperidin-2-one, are prepared via a phthalimide deprotection and stereoselective cyclization of the free amine toward an activated ester. This cyclization strategy allows for the preparation of both enantiomers through steric or electronic controls. Conversion of intermediate γ- or δ-lactams into mesylates, nucleophilic substitution, and ring opening led to the formation of γ2,2 and δ2,2-serine, -azido, and -cysteine analogues. General application of the cyclization strategy was found to be limited by sterics imposed by the neopentyl intermediate resulting in longer reaction times and inability to substitute some nucleophiles. The esterification of oxidized glutathione with thionyl chloride and various alcohols was monitored for completeness using electrospray ionization mass spectrometry. Oxidized glutathione was found to be highly compatible with an excess of methanol and ethanol, but slow and incomplete with 2-propanol. The thionyl chloride esterification was applied to other small peptides to evaluate the limitations with various amino acid side chains. The results show incompatibilities with peptides containing both serine and cysteine but well tolerated with the remaining natural amino acids

Efficient Esterification of Oxidized l-Glutathione and Other Small Peptides

xidized l-glutathione was esterified to the tetra methyl ester using thionyl chloride in methanol solvent. Other alcohols were tested and the reaction progress was monitored via ESI-MS. This procedure proved to be compatible with other small peptides not containing serine and cysteine residues. In contrast to previously reported methods this procedure provided convenient access to esterified peptides requiring no purification, extended reaction times, or complicated reaction setups

An Enantiodivergent Synthesis of C\u3csup\u3eα\u3c/sup\u3e-Methyl Nipecotic Acid Analogues From δ-Lactam Derivatives Obtained Through a Highly Stereoselective Cyclization Strategy

A stereoselective and enantiodivergent strategy for the construction of δ-lactams is described. The strategy utilizes chiral malonic esters prepared from enantiomerically enriched mono esters of disubstituted malonic acid. A cyclization occurs with the selective displacement of a substituted benzyl alcohol as the leaving group. The resulting δ-lactams are then converted into nipecotic acid analogues using straightforward transformations. The resulting nipecotic acid analogues proved capable organocatalysts in Mannich reactions

Endophytic fungi in Canada wild rye in natural grasslands

Some grasses harbor endophytic fungi living in intercellular spaces in the leaves, stems and reproductive organs. The fungi can dramatically affect the physiology and ecology of plants. For example, fungi may produce toxins that deter herbivores and they may alter the water status of the plant to increase drought tolerance. The distribution of fungal infection in natural plant populations is unknown for many host species. We investigated the occurrence of endophytic fungi in Elymus canadensis L. (Canada wild rye) from 13 remnant prairie sites in the midwest and 23 sites in the southern Great Plains. Collections of plant tissue came from Nebraska, Kansas, Minnesota, Iowa, Missouri, Illinois, Oklahoma, and Texas. All midwest plants were grown in a common garden site in eastern Nebraska. Seeds collected from Oklahoma and Texas accessions were planted in the greenhouse. At least 3 tillers from 2 plants of each accession were screened for endophytes, using light microscopy. The endophytic fungus was found in seed of all accessions and in plants from all but 4 accessions. The functional significance of the fungus is unclear, but it may affect plants by enhancing productivity or deterring herbivores. The widespread occurrence of endophytic fungi in natural populations of E. canadensis suggests that the plant-fungal association may be long-standing and important in the evolution and success of this native prairie species. Algunos zacates albergan hongos endofiticos que viven en los espacios intracelulares de las hojas, tallos y órganos reproductivos. Los hongos pueden afectar dramáticamente la fisiología y ecología de las plantas. Por ejemplo, el hongo puede producir toxinas que desalientan a los herbívoros y ellos pueden alterar el estado hídrico de la planta para incrementar la tolerancia a sequía. La distribución de la infección fungal en poblaciones de plantas naturales es desconocida para muchas de las especies hospederas. Investigamos la ocurrencia de hongos endofiticos en Elymus canadensis L. (Canada wild rye) en 13 sitios de pradera en el medio oeste y en 23 sitios en las Grandes Planicies del Sur. Colecciones de tejidos de plantas arribaron de Nebraska, Kansas, Minnesota, Iowa, Missouri, Illinois, Oklahoma, and Texas. Todas las plantas provenientes del medio oeste se cultivaron en un sitio de jardín común en el este de Nebraska. Las semillas colectadas de las entradas de Oklahoma and Texas se plantaron en invernadero. Al menos 3 hijuelos de dos plantas de cada entrada se inspeccionaron mediante luz microscópica para determinar los endófitos. El hongo endófito se encontró en las semillas de todas las entradas y en plantas de todas menos 4 entradas. El significado funcional del hongo no es claro, pero puede afectar las plantas aumentando su productividad o desalentando a los herbívoros. La ocurrencia tan amplia y dispersa de los hongos endofiticos en las poblaciones naturales de E. Canadiensis sugiere que la asociación planta-hongo puede ser importante en la evolución y éxito de esta especie nativa de las prader

Concert recording 2018-11-02

[Track 1]. My house from Matilda / Tim Minchin -- [Track 2]. Everybody loves Louis from Sunday in the park with George / Stephen Sondheim -- [Track 3]. Per la gloria d\u27adorarvi / Giovanni Battista Bononcini -- [Track 4]. The vagabond / Ralph Vaughan Williams -- [Track 5]. Se tu m\u27ami / Alessandro Parisotti -- [Track 6]. Die Hölle Rache kocht from The magic flute / Wolfgang Amadeus Mozart -- [Track 7]. Dans un boire solitaire / Wolfgang Amadeus Mozart -- [Track 8]. Love\u27s philosophy / Roger Quilter -- [Track 9]. Comme raggio di sol / Antonio Caldara -- [Track 10]. The vagabond / Ralph Vaughan Williams -- [Track 11]. Sognai / Francesco Schira -- [Track 12]. Fair Robin I love from Tartuffe / Kirke Mechem -- [Track 13]. Sonntag, op. 47, no. 3 / Johannes Brahms -- [Track 14]. O del mio amato ben / Stefano Donaudy -- [Track 15]. Spring / Dominick Argento -- [Track 16]. Gott im Frühling, D. 448 / Franz Schubert -- [Track 17]. Vaga luna, che inargent / Vincenzo Bellini -- [Track 18]. The Salley gardens / Benjamin Britten -- [Track 19]. Three browning songs, op. 44. I. The year\u27s at the spring II. Ah, love, but a day III. I send my heart up to thee / Amy Beach -- [Track 20]. From Dichterliebe, op. 48. 6. Im Rhein, im heiligin Strome 7. Ich grolle nicht 8. Und wüssten\u27s die Blumen, die kleinen 9. Das ist ein Flöten und Geigen / Robert Schumann -- [Track 21]. Thy hand, Belinda from Dido and Aeneas / Henry Purcell -- [Track 22]. Cowboy songs. I. Bucking bronco II. Lift me into heaven slowly III. Billy the kid / Libby Larsen

Zebrafish orthologs of human muscular dystrophy genes

BACKGROUND: Human muscular dystrophies are a heterogeneous group of genetic disorders which cause decreased muscle strength and often result in premature death. There is no known cure for muscular dystrophy, nor have all causative genes been identified. Recent work in the small vertebrate zebrafish Danio rerio suggests that mutation or misregulation of zebrafish dystrophy orthologs can also cause muscular degeneration phenotypes in fish. To aid in the identification of new causative genes, this study identifies and maps zebrafish orthologs for all known human muscular dystrophy genes. RESULTS: Zebrafish sequence databases were queried for transcripts orthologous to human dystrophy-causing genes, identifying transcripts for 28 out of 29 genes of interest. In addition, the genomic locations of all 29 genes have been found, allowing rapid candidate gene discovery during genetic mapping of zebrafish dystrophy mutants. 19 genes show conservation of syntenic relationships with humans and at least two genes appear to be duplicated in zebrafish. Significant sequence coverage on one or more BAC clone(s) was also identified for 24 of the genes to provide better local sequence information and easy updating of genomic locations as the zebrafish genome assembly continues to evolve. CONCLUSION: This resource supports zebrafish as a dystrophy model, suggesting maintenance of all known dystrophy-associated genes in the zebrafish genome. Coupled with the ability to conduct genetic screens and small molecule screens, zebrafish are thus an attractive model organism for isolating new dystrophy-causing genes/pathways and for use in high-throughput therapeutic discovery

Transcriptional Profiling of Aging in Human Muscle Reveals a Common Aging Signature

We analyzed expression of 81 normal muscle samples from humans of varying ages, and have identified a molecular profile for aging consisting of 250 age-regulated genes. This molecular profile correlates not only with chronological age but also with a measure of physiological age. We compared the transcriptional profile of muscle aging to previous transcriptional profiles of aging in the kidney and the brain, and found a common signature for aging in these diverse human tissues. The common aging signature consists of six genetic pathways; four pathways increase expression with age (genes in the extracellular matrix, genes involved in cell growth, genes encoding factors involved in complement activation, and genes encoding components of the cytosolic ribosome), while two pathways decrease expression with age (genes involved in chloride transport and genes encoding subunits of the mitochondrial electron transport chain). We also compared transcriptional profiles of aging in humans to those of the mouse and fly, and found that the electron transport chain pathway decreases expression with age in all three organisms, suggesting that this may be a public marker for aging across species

Concert recording 2018-04-16

[Track 1]. Music for a while / Henry Purcell -- [Track 2]. Lachen und Weinen / Franz Schubert -- [Track 3]. Sebben crudele / Antonio Caldara -- [Track 4]. Money, o! / Michael Head -- [Track 5]. Les Berceaux / Gabriel Fauré -- [Track 6]. Music I heard with you / Richard Hageman -- [Track 7]. Die Forelle / Schubert -- [Track 8]. Take, o take those lips away / Roger Quilter -- [Track 9]. La pastorella delle Alpi / Gioachino Rossini -- [Track 10]. Pastorale / Georges Bizet -- [Track 11]. Laudamus te from Mass in C minor, K. 427 / Wolfgang Amadeus Mozart -- [Track 12]. Winter / Dominick Argento -- [Track 13]. From Canciones clásicos españos. I. La mi sola, Laureola II. Al amor III. ¿Corazón porqué pasáis IV. Chiquitita la novia / Fenando Obradors -- [Track 14]. From Lieder und Gesänge aus Wilhelm Meister, op. 98a. Kennst du das Land Nur Wer die Sehnsucht kennt Heiss mich nicht reden, heiss mich schweigen / Robert Schumann -- [Track 15]. Non t\u27accostar all\u27urna / Schubert Non t\u27accostar all\u27urna / Giuseppe Verdi -- Плач об умершем младенце / Dmitri Shostakovich -- [Track 16]. Airs Chantés. I. Air Romantique II. Air Champêtre III. Air Grave IV. Air Vif / Francis Poulenc